Trial Outcomes & Findings for Obeticholic Acid in Bile Acid Diarrhoea (NCT NCT01585025)

Results Overview

The primary outcome measure is the change over 2 weeks in fasting serum fibroblast growth factor (FGF19) in 3 groups of patients: primary bile acid diarrhoea, secondary bile acid diarrhoea, and a control population of patients with chronic diarrhoea but with normal bile acid retention.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Day 0, Day 15

Results posted on

2023-03-10

Participant Flow

Participant milestones

Participant milestones
Measure	Primary BAD Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Overall Study STARTED	10	13	12
Overall Study COMPLETED	10	10	8
Overall Study NOT COMPLETED	0	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Primary BAD Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Overall Study Withdrawal by Subject	0	3	4

Baseline Characteristics

Obeticholic Acid in Bile Acid Diarrhoea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Primary BAD n=10 Participants Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD n=10 Participants With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls n=8 Participants Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection	Total n=28 Participants Total of all reporting groups
Age, Continuous	47 years n=5 Participants	45 years n=7 Participants	39 years n=5 Participants	41 years n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Region of Enrollment United Kingdom	10 participants n=5 Participants	10 participants n=7 Participants	8 participants n=5 Participants	28 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 0, Day 15

The primary outcome measure is the change over 2 weeks in fasting serum fibroblast growth factor (FGF19) in 3 groups of patients: primary bile acid diarrhoea, secondary bile acid diarrhoea, and a control population of patients with chronic diarrhoea but with normal bile acid retention.

Outcome measures

Outcome measures
Measure	Primary BAD n=10 Participants Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD n=10 Participants With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls n=8 Participants Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Changes in Fasting FGF19	71 percentage increase of baseline Interval 9.0 to 102.0	25 percentage increase of baseline Interval -6.0 to 140.0	130 percentage increase of baseline Interval -14.0 to 304.0

SECONDARY outcome

Timeframe: Day 0, Day 15

Change in dynamic response of FGF19 in 6 hours following OCA administration; at start and end of 15 day OCA test period.

Outcome measures

Outcome measures
Measure	Primary BAD n=10 Participants Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD n=10 Participants With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls n=8 Participants Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Changes in Non-fasting Response of FGF19 to OCA	11.6 percentage change Interval -23.6 to 57.8	14.6 percentage change Interval -22.7 to 49.0	32.4 percentage change Interval 15.1 to 38.4

SECONDARY outcome

Timeframe: Day 0, Day 15

Population: Missing data in Primary BAD

Change in fasting 7α-hydroxy-4-cholesten-3-one before and after 15 day administration of OCA.

Outcome measures

Outcome measures
Measure	Primary BAD n=8 Participants Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD n=10 Participants With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls n=8 Participants Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Changes in Fasting 7α-hydroxy-4-cholesten-3-one	-11.5 microgram/L Interval -30.0 to -3.5	-27.5 microgram/L Interval -56.3 to 0.0	-6.5 microgram/L Interval -11.5 to -1.5

SECONDARY outcome

Timeframe: Day 0, Day 15

Dynamic changes of total bile acids over 6 hour period following OCA administration before and after 15 day OCA period.

Outcome measures

Outcome measures
Measure	Primary BAD n=10 Participants Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD n=10 Participants With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls n=8 Participants Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Changes in Serum Total Bile Acids.	-18.1 micromol/L Interval -33.0 to -5.5	-2.0 micromol/L Interval -17.5 to 0.08	-15.5 micromol/L Interval -17.9 to -14.0

SECONDARY outcome

Timeframe: Week 2, Week 4

Population: Missing data in Idiopathic diarrhoea controls

Change in total number of stool episodes reported per week between week 2 (baseline) and week 4 (week 2 of treatment)

Outcome measures

Outcome measures
Measure	Primary BAD n=10 Participants Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD n=10 Participants With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls n=7 Participants Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Changes in Stool Frequency	-4.5 stools per week Interval -9.3 to -1.5	-2.5 stools per week Interval -15.8 to 1.8	3.0 stools per week Interval -3.0 to 7.0

SECONDARY outcome

Timeframe: Week 2, Week 4

Population: Missing data in Idiopathic diarrhoea controls

Change in mean stool form reported per week between week 2 (baseline) and week 4 (week 2 of treatment) using the Bristol Stool Form Scale (range of scores 1 to 7). High scores are a worse outcome (7=liquid stools).

Outcome measures

Outcome measures
Measure	Primary BAD n=10 Participants Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD n=10 Participants With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls n=7 Participants Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Changes in Mean Stool Form	-0.71 Score on Bristol scale Interval -1.54 to 0.1	-0.38 Score on Bristol scale Interval -0.91 to -0.18	-0.46 Score on Bristol scale Interval -0.91 to 0.86

SECONDARY outcome

Timeframe: Week 2, Week 4

Population: Missing data in Idiopathic diarrhoea controls

Change in index calculated on a weekly basis, between week 2 (baseline) and week 4 (week 2 of treatment). Index calculated as (\[weekly stool frequency x mean Bristol Stool Form Scale score\] = Loperamide use \[weekly mg x 3\]). Individual scores ranged from 25 to 1095, with higher scores being worst.

Outcome measures

Outcome measures
Measure	Primary BAD n=10 Participants Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD n=10 Participants With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls n=7 Participants Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Change in Stool Index	-37.5 index score Interval -52.3 to -22.8	-32.5 index score Interval -158.6 to -13.4	-5.5 index score Interval -30.0 to 20.0

Adverse Events

Primary BAD

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Secondary BAD

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Idiopathic Diarrhoea Controls

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Primary BAD n=10 participants at risk Defined as SeHCAT \<10% without other causes such as Crohn's disease and/or ileal resection	Secondary BAD n=10 participants at risk With Crohn's disease or ileal resection	Idiopathic Diarrhoea Controls n=8 participants at risk Chronic diarrhoea with SeHCAT \>15% and no Crohn's or ileal resection
Nervous system disorders Headache	0.00% 0/10 • Data were collected over the 6 weeks of the trial	20.0% 2/10 • Number of events 2 • Data were collected over the 6 weeks of the trial	12.5% 1/8 • Number of events 1 • Data were collected over the 6 weeks of the trial
Gastrointestinal disorders Constipation/abdominal pain	0.00% 0/10 • Data were collected over the 6 weeks of the trial	10.0% 1/10 • Number of events 1 • Data were collected over the 6 weeks of the trial	0.00% 0/8 • Data were collected over the 6 weeks of the trial

Additional Information

Prof Julian Walters

Imperial College London

Phone: +442033132361

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place